tbuckley/cabot-search huggingface dataset:
A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor–Positive Recurrent Endometrial Cancer
Authors: Panagiotis A. Konstantinopoulos, Elizabeth K. Lee, Niya Xiong, Carolyn Krasner, Susana Campos, David L. Kolin, Joyce F. Liu, Neil Horowitz, Alexi A. Wright, Sara Bouberhan, Richard T. Penson, Oladapo Yeku, Brittany Bowes, Hope Needham, Martin Hayes, Hannah Sawyer, Madeline Polak, Meghan Shea, Su-Chun Cheng, Cesar Castro, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2022)

Estrogen receptor (ER)-positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/β-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting.We conducted a phase II, two-stage study of letrozole/abemaciclib in recurrent ER-positive EC. Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies; prior hormonal therapy was allowed. Primary end points were objective response rate by RECIST 1.1 and progression-free survival (PFS) rate at 6 months.At the data cutoff date (December 03, 2021), 30 patients (28 with endometrioid EC) initiated protocol therapy; 15 (50%) patients had prior hormonal therapy. There were nine total responses (eight confirmed), for an objective response rate of 30% (95% CI, 14.7 to 49.4), all in endometrioid adenocarcinomas. Median PFS was 9.1 months, PFS at 6 months was 55.6% (95% CI, 35.1 to 72), and median duration of response was 7.4 months. Most common ≥ grade 3 treatment-related adverse events were neutropenia (20%) and anemia (17%). Responses were observed regardless of grade, prior hormonal therapy, mismatch repair, and progesterone receptor status. Exploratory tumor profiling revealed several mechanistically relevant candidate predictors of response (CTNNB1, KRAS, and CDKN2A mutations) or absence of response (TP53 mutations), which require independent validation.Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER positive endometrioid EC.
Multifunctional nanoprobes for macrophage imaging
Authors: Hongping Deng, None Li Xu, Jingxuan Ju, Xuan Mo, Guangbo Ge, Xinyuan Zhu
Journal: Biomaterials (2022)

Imaging and tracking macrophage behaviors in vivo are essential to reveal its biological function and fate in various diseases. Small molecular probes suffer from poor macrophage targeting and retention, rapid clearance, and deficient metabolizing stability. To overcome these limitations, a variety of functional nanoprobes have been developed for targeted imaging of macrophages in divergent diseases such as cancer, atherosclerosis and obesity. Generally, nanoprobes are functionalized with targeting peptides, ligands or antibodies to fulfill high macrophage affinity. In this review, the most recent advances of nanoprobes for imaging macrophages in vivo and ex vivo are systematically summarized. The challenges and perspectives of precisely imaging macrophages with improved signal-to-background ratios via nanoprobes are further discussed.
Organ dysfunction, thrombotic events and malignancies in patients with idiopathic multicentric castleman disease: a population-level US health claims analysis
Authors: Sudipto Mukherjee, Karan Kanhai, David Kauffman, Rabecka Martin, Jeremy S. Paige, Anirvan Ghosh, Hannah Kannan, Francis Shupo, David C. Fajgenbaum
Journal: Leukemia (2022)

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by a hyperinflammatory state driven primarily by hypercytokinemia, particularly interleukin-6 (IL-6) [1][2][3].iMCD patients have historically poor outcomes [4], particularly among patients who were not properly treated [5].Among several factors, one potential reason for delayed treatment initiation could be a lack of understanding of the clinical trajectory of iMCD patients regarding the development of disease-associated morbidities over time.A better understanding of the natural history of iMCD, particularly the evolution and prevalence of morbidities, will be helpful for making timely decisions about appropriate treatment and potentially mitigate morbidity burden in these patients.The primary objective of this study was to evaluate the pattern of morbidities and their prevalence in iMCD patients using a nationally representative health claims dataset.We additionally analyzed healthcare utilization of iMCD patients by evaluating length of hospital stays and visits to emergency departments by these patients.Anonymized longitudinal patient data were sourced from Truven MarketScan® Research Databases (IBM), covering 235 million US citizens (commercially-insured, on Medicare, or Medicaid) from January 2006 to December 2020 [6].All eligible iMCD patients were identified using a previously validated claimsbased algorithm that in addition to CD-specific ICD-10 diagnosis code (D47.Z2), required negative HHV-8 and HIV status, and presence of corresponding diagnostic or laboratory claims for ≥2 minor criteria, consistent with published diagnostic criteria recommendations for iMCD [7,8].A patient's index diagnosis date (IDD) was defined as the first date of the D47.Z2 diagnosis claims code when available or the previous nonspecific ICD-9-CM code for enlargement of lymph nodes previously used for CD (785.6), whichever appeared first.Morbidities occurring in iMCD patients were grouped in three categories and identified using ICD9/10 diagnosis codes: (1) Organ dysfunction and thrombotic events including heart failure, liver dysfunction, renal dysfunction,
In Silico–Based Approach to the Discovery of New Antigens in Membranous Nephropathy
Authors: Mayumi Takahashi-Kobayashi, Joichi Usui, Kunio Kawanishi, Kunihiro Yamagata
Journal: Journal of the American Society of Nephrology (2022)

Sealfon et al.1 recently reported the molecular characterization of membranous nephropathy (MN) using the Nephrotic Syndrome Study Network (NEPTUNE) cohort and the European Renal cDNA Bank (ERCB) cohort. They took a machine-learning approach to identify molecular characteristics of MN, but we believe that in silico–based approaches can also provide a clue to discover new MN antigens. Eight MN antigens have been identified to date, starting with PLA2R,2 but others may exist. Rather than the NEPTUNE and ERCB databases used by Sealfon et al., we used Nephroseq, a web-based dataset that provides information on genome-wide gene expression,3 to examine transcription patterns in various types of kidneys. We applied Nephroseq according to the following protocol. ( Using the Ju CKD Glom dataset, place the genes with higher expression in MN than in other diseases in order, from the top rank to 100. By doing so, we unexpectedly observed that three of the eight known MN antigens were ranked in the top 0.6% when we compared MN with other renal diseases: NELL1 (ranked first, P=7.9 × 10−10), PCDH7 (ranked 27th, P=2.2 × 10−6), and PLA2R (ranked 110th, P=4.7 × 10−5). ( Check where in the cell each gene is expressed, and identify and retain genes encoding secreted and membrane-bound proteins as candidates; exclude others. ( Using the Ju CKD Glom dataset, exclude genes whose expression levels are lower in MN compared with in healthy living donors or in patients with minimal change nephrotic syndrome. ( Using the Lindenmeyer Normal Tissue Panel dataset, compare expression levels in glomeruli to those in tubulointerstitium, and exclude genes whose expression is higher in tubulointerstitium than in glomeruli. ( Search the encoded proteins' characteristics and check the staining patterns in the kidney in the Human Protein Atlas, as done by Sealfon et al.1 ( Perform immunofluorescence staining. After this procedure, we observed that eight of the top 100 genes remaining (TSPAN6, FAM189A2, PAMR1, AMIGO2, ANXA1, LHFP, PON2, P4HTM) encode proteins in the glomerulus. We performed immunofluorescence staining for these candidate proteins in MN tissue samples (n=19) that were negative for PLA2R, THSD7A, and NELL1. All eight candidates were negative in immunohistochemistry, but, notably, five (TSPAN6, PAMR1, AMIGO2, ANXA1, PON2) were also listed in the Sealfon group's MN-specific gene list. This type of unprecedented approach has the potential to open new avenues to MN antigen exploration. Disclosures K. Yamagata reports receiving honoraria from Astellas, AstraZeneca, Kyowa-Kirin, Mochida, Otsuka, and Tanabe-Mitsubishi; having consultancy agreements with Chugai Co. Ltd. and Japan Medtronic Co. Ltd.; and receiving research funding from Kyowa-Kirin and Tanabe-Mitsubishi. All remaining authors have nothing to disclose. Funding This work was supported by Japan Society for the Promotion of Science KAKENHI grants JP22J20394, JP19KK0216, and JP21H02822.
Editorial Correspondence.
Authors: W F Westmoreland
Journal: JAMA (1895)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Modulation of lipid peroxidation and energy metabolism in the gastric mucosa as a mechanism ofantiulcer activity of placental cryoextract in the healing of stress-induced ulcers
Authors: I.V. Koshurba, F.V. Hladkykh, M.O. Chyzh
Journal: GASTROENTEROLOGY (2022)

Background. Peptic ulcer disease has a leading place in the overall structure of digestive diseases: its prevalence is 6.00–10.0% of the population in developed countries, and mortality ranges from 6 to 9.7 per 100 thousand population. An important etiological factor of this pathology is the neuropsychological background, primarily stress, which under repeated exposure becomes the initiating factor of physiological imbalance between the elements of aggression and protection of the gastric mucosa. The purpose was to establish the mechanisms of the protective activity of placental cryoextract based on the biochemical indicators of lipid peroxidation and antioxidant protection in the gastric mucosa on a model of stress-induced erosive-ulcerative damage. Materials and methods. Studies were performed on 28 nonlinear laboratory male rats weighing 200–220g. Stress-induced gastric ulcer was modeled under water-immobilization stress in rats according to the K.Y. Takagi etal. In the gastric mucosa, the content of reactants with thiobarbituric acid was determined spectrophotometrically by the method of T. Asakawa etal., catalase activity— spectrophotometrically by the method of M.A.Korolyuk etal., the content of reduced glutathione— spectrophotometrically by the method of E.D. Beutler etal., the level of adenyl nucleotides was determined using chromatographic method. Energy charge was calculated by D.E. Atkinson equation. Results.The prophylactic five-day use of placental cryoextract led to a decrease in the severity of stress-induced lipid peroxidation and energy imbalance in the gastric mucosa. Thus, it was found that rats who received placental cryoextract had a statistically significant (p&lt;0.001) increase in adenosine triphosphate content by 73.3%, an increase in adenosine diphosphate (p&lt;0.001) by 37.3% and a decrease in adenosine monophosphate (p&lt;0.001) by 47.6% that led to an increase in energy charge (p&lt;0.001) by 35.1% compared to rats exposed to water-immobilization stress without correction (control group). It was shown that the use of placental cryoextract led to a statistically significant (p&lt;0.001) increase in the antioxidant-prooxidant index by 3.1 times versus control group, which was (26.60±0.96) and (8.60±0.43), respectively. Conclusions. Prophylactic five-day administration of placental cryoextract leads to the restoration of balance in the system of adenyl nucleotides and, accordingly, to a statistically significant (p&lt;0.001) increase in the energy charge by 35.1% compared to the control animals. Inhibition of stress-induced hyperactivation of lipid peroxidation in the gastric mucosa is one of the mechanisms of its antiulcer activity.
Fasting and the Precipitation of Labor
Authors: Michael Kaplan
Journal: JAMA (1983)

We analyzed the effect of a 24-hour total food and water fast on the spontaneous onset of labor by studying the effect of the fast of Yom Kippur on Jewish pregnant women in Jerusalem. The mean baseline number of deliveries for our study period was 11.9 and 12.0 for 1981 and 1982, respectively. The number of deliveries on Yom Kippur was not significantly different from the mean. However, the number of deliveries for the 24-hour period after termination of the fast was 22 and 26 for 1981 and 1982, respectively. This difference attained statistical significance. While the clinical implications are not yet clear, a special risk may exist for women with a tendency toward early delivery should they undertake a 24-hour fast. (<i>JAMA</i>1983;250:1317-1318)
Corrigendum to ‘The epidemic of multidrug resistant tuberculosis in China in historical and phylogenetic perspectives’ [Journal of Infection, Volume 80, Issue 4 (2020) Pages 444-453]
Authors: Yang Zhou, Richard Anthony, Shengfen Wang, Xichao Ou, Dongxin Liu, Yanlin Zhao, Dick van Soolingen
Journal: Journal of Infection (2022)
1619P Assessment of the pharmacokinetic interaction of enzalutamide with oxycodone in men with prostate cancer: The ENZYME study
Authors: S.E.H. Detert Oude Weme, W.L. Vervenne, A.L.T. Imholz, R.G.H.M. Cremers, I.R.F. van Berlo-van de Laar, F.G.A. Jansman, G.E. Benoist
Journal: Annals of Oncology (2022)
1422P Validation of the prognostic value of the early modeled longitudinal PSA kinetics (KELIM and KPROD) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with taxanes in FIRSTANA
Authors: A. Carrot, S. Oudard, O. Colomban, K. Fizazi, O. Sartor, G. Freyer, B. You
Journal: Annals of Oncology (2022)
Highlights from Recent Cancer Literature
Journal: Cancer Research (2014)

EFA6B-A Novel Antagonist of Breast CancerTriple-negative breast cancer (TNBC) shows low overall survival and high recurrence, and these cancers are enriched for a new claudin-low breast cancer subtype.EFA6B (Exchange Factor for ARF6 isoform B, PSD4) is a guanine nucleotide exchange factor for the Ras superfamily protein ARF6 that helps assemble tight junctions.Low levels of EFA6B were also enriched in aggressive triple-negative and claudin-low breast cancer subtypes.Zangari and colleagues observed that EFA6B was required to maintain apico-basal cell polarity.Downregulating EFA6B expression correlated with a mesenchymal phenotype, and ectopic expression inhibited TGFb-induced epithelial-mesenchymal transition (EMT).EFA6B repression was also associated with loss of tight junction components and with increased EMT, cancer stemness, and poor prognosis in human breast tumor samples.Thus, EFA6B represents a novel therapeutic target that antagonizes early stages of breast cancer by hampering tight junction disassembly and loss of epithelial polarity.
1413P Tumor transcriptomic profiling of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) who do not achieve optimal PSA response to intensified androgen deprivation therapy (ADT-I)
Authors: V. Mathew Thomas, B. Chigarira, N. Sayegh, E.J. Hernandez, N. Tripathi, S. Adidam Kumar, D. Goel, C. Tandar, T.R. Mcfarland, M. Yandell, R. Nussenzveig, D. Sirohi, U. Swami, B.L. Maughan, N. Agarwal
Journal: Annals of Oncology (2022)
1423TiP CYCLONE 3: A phase III, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone plus prednisone in men with high-risk metastatic hormone-sensitive prostate cancer (mHSPC)
Authors: R.R. McKay, N. Agarwal, N. Matsubara, J.M. Piulats Rodriguez, M.R. Smith, T. Todenhöfer, T. Zhang, A.V. Balar, C. Schaverien, S. Sherwood, E. Johnston, A. Lithio, K. Nacerddine, C.J. Sweeney
Journal: Annals of Oncology (2022)
1418P Extensive alteration of androgen precursor levels after castration in prostate cancer patients and their association with active androgen level: Importance for treatment intensification
Authors: F. Pouliot, M. Rouleau, B. Neveu, P. Caron, F. Morin, P. Toren, L. Lacombe, V. Turcotte, E. Lévesque, C. Guillemette
Journal: Annals of Oncology (2022)
1419P Radiobiological parameters for the assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer
Authors: J. Hu, S. Xue, L. Mercolli, S. Hasan, A. Rominger, A. Afshar-Oromieh, K. Shi
Journal: Annals of Oncology (2022)
1524P Epidemiology and demography of gynecological sarcoma: Results of the prospective intergroup registry for gynecological sarcoma REGSA (NOGGO RU1)
Authors: E. Roser, A-S. Noack, D. Zocholl, S. Kommoss, P. Harter, M. Kalder, E.K. Egger, P. Buderath, C. Marth, U. Ulrich, M. Klar, M. Weigel, L. Traub, H-G. Strauß, L. Hanker, M. Pölcher, P. Wimberger, F. Beck, K. Pietzner, J. Sehouli
Journal: Annals of Oncology (2022)
1417P Mixed treatment comparisons evaluating contemporary therapies in metastatic castration sensitive prostate cancer (mCSPC): A living systematic review
Authors: I.B. Riaz, S.A.A. Naqvi, H. He, N. Asghar, R. Siddiqi, K.Z.R. Khakwani, H. Liu, S.A. Hussain, P. Singh, M. Murad, A.H. Bryce
Journal: Annals of Oncology (2022)
1528TiP A phase II/III study evaluating the efficacy and safety of unesbulin in advanced leiomyosarcoma (SUNRISELMS)
Authors: M. Ingham, J-Y. Blay, J. Baird, D. D'Silva, K. O'Keefe, R. Kong, R. Spiegel, M. Wahba, M. Weetall
Journal: Annals of Oncology (2022)
1421P Effect of abiraterone-prednisone in metastatic castration-sensitive prostate cancer (mCSPC) with neuroendocrine and very high-risk features in the PEACE-1 trial
Authors: A. Bernard-Tessier, M. Cancel, B. Tombal, G. Roubaud, J. Carles Galceran, A. Flechon, R.S. McDermott, S. Supiot, D.R. Berthold, R. Philippe, G. Kacso, G. Gravis Mescam, F. Calabrò, J.F. Berdah, A. Hasbini, F. Ricci, C. Hennequin, H. Ribault, S. Foulon, K. Fizazi
Journal: Annals of Oncology (2022)
1526TiP TOLERANCE: An EORTC STBSG-QLG-ETF 3-arm randomized study on health-related quality of life of elderly patients with advanced soft tissue sarcoma undergoing doxorubicin alone three weekly or doxorubicin weekly or cyclophosphamide plus predniso(lo)ne treatment
Authors: W.T.A. van der Graaf, G. Marquina, A. Brunello, C. Coens, G. Farro, L. Meirsman, O. Husson
Journal: Annals of Oncology (2022)
1621P miRNA signature as early predictor of hyponatremia and survival in lung cancer: Preliminary results from the ISA retrospective study
Authors: G. Mentrasti, E. Ambrosini, L. Giuliani, N. Chiodi, C. Liguori, M. Gualtieri, F. Bianchi, F. Barbisan, G. Goteri, M.B.L. Rocchi, R. Berardi
Journal: Annals of Oncology (2022)
1527TiP CONGRATS-combination of nivolumab plus relatlimab in patients with advanced or metastatic soft-tissue sarcoma: A proof-of-concept randomized phase II study
Authors: M. Spalato Ceruso, S. Albert, A. Italiano, M. Toulmonde, S. Cousin, T. Grellety, J-Y. Blay, B. Verret, C. Auzanneau, V. Valade, L. Poignie, B. Lortal, M. Kind, F. Le Loarer, M. Pulido
Journal: Annals of Oncology (2022)
1618P Impact of body composition phenotypes on outcome of non-small cell lung cancer patients treated with immunotherapy
Authors: I. Trestini, A. Caldart, A. Dodi, M. Cintoni, M. Sposito, L. Belluomini, J. Menis, E. Vita, I. Sperduti, A. Drudi, G. Aluffi, M. Todesco, D. Tregnago, A. Avancini, M. D'Onofrio, M.C. Mele, G. Tortora, M. Milella, E. Bria, S. Pilotto
Journal: Annals of Oncology (2022)
1620P Return to work trajectories after early breast cancer diagnosis: A population-based cohort study in the French National Healthcare Insurance database
Authors: R. Varnier, A. Moskal, A.L. Dima, C. Bodelet, J. Peron, M. Lamort-Bouché, J.-B. Fassier, M. Viprey
Journal: Annals of Oncology (2022)
1420P The pharmacokinetics and the pharmacodynamic effect of ODM-208, an inhibitor of cholesterol side-chain cleavage enzyme (CYP11A1)
Authors: A. Bernard-Tessier, P. Nykanen, T. Utriainen, N. Cook, P. Barthelemy, C. Baldini, N. Peters, T. Ikonen, P. Pohjanjousi, M. Karimaa, J. Malkki, P.T. Toivanen, C. Garratt, K. Fizazi
Journal: Annals of Oncology (2022)
Minoxidil and Cardiac Enlargement
Authors: David S. Svahn
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The article on longterm use of minoxidil by Mitchell and Pettinger (239:2131, 1978) describes nine of 17 current patients with an increase in heart size. Four might have been due to poor blood pressure (BP) control (and presumed progressive left ventricular enlargement), but in five there was no good explanation. I have followed up only one patient who was receiving minoxidil, but an apparent increase in heart size also developed in this man, which began within a week of starting minoxidil therapy in 1973. Within 18 months and despite absence of symptoms and with excellent BP control, the cardiac outline had reached impressive proportions. Echocardiography showed a pericardial effusion. Cardiac catheterization (done also because of reports of pulmonary hypertension with minoxidil therapy) showed no hemodynamic abnormalities. Pericardicentesis was unrevealing of infection or inflammation, though the fluid was reported as serosanguineous, and the protein level was 3.8 g/dl.
1617P Impact of nutritional counselling (NC) on CT-based body composition in patients with oncogene addicted advanced non-small cell lung cancer (aNSCLC)
Authors: A.M. Morelli, M. Bungaro, I. Capizzi, E. Parlagreco, F. Solitro, L. Eletti, S. Martinetto, A. Veltri, M. Tinivella, P. Pedrazzoli, R. Caccialanza, V. Bertaglia, E. Capelletto, M.L. Reale, S. Novello, M. Tampellini
Journal: Annals of Oncology (2022)